Brain protection in neuropsychiatric disorders: Past, present and future challenges

Abstract

Brain- or neuroprotection is any therapy that prevents, retards, or reverses neuronal cell death resulting from neurodegenerative processes. In the past neuroprotection has been an active field of research in medical areas ranging diversely from neurology through cardiology to ophthalmology. However, it has only been in recent years that the psychiatric community began to sit up and take notice - be it due to improved technological imaging capabilities or because of the growing dissatisfaction with current pharmacological treatments (particularly in schizophrenia) regarding negative and cognitive symptom domains, second generation antipsychotics included. Mounting evidence indicates that neuropsychiatric disorders such as Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, schizophrenia, mood and cognitive disorders all have a neurodegenerative component proposed to be due to various mechanisms including oxidative stress, mitochondrial dysfunction, excitotoxicity, myelin dysfunction and apoptosis to name just a few. New and improved imaging techniques combined with advanced cognitive testing continue to help us assess this degenerative component. However, despite considerable research effort, clinical trials in search of an agent that can effectively protect the brain of patients with schizophrenia, mood and cognitive disorders have been largely disappointing as of yet. Thus, it would seem that the continuing search for neuroprotective factors in psychiatry would be especially pertinent for finding novel treatments and augmentation strategies - not only for treating active symptoms, but also for slowing down disease progression and possibly even providing primary prevention in recognized prodromal states. As of now several drugs, hormones, neurosteroids, vitamins as well as various other substances have been studied regarding their neuroprotective properties in psychiatric disorders, with variable amounts of success. Other neuroprotective approaches being studied include the utilization of nanotechnological scientific advances as well as neuromodulatory techniques (such as transcranial magnetic stimulation, vagal nerve stimulation and deep brain stimulation). In this chapter we will review the trends in psychiatric neuroprotection in the past and the present in addition to raising questions for future directions and challenges. The present overview will cover the evidence concerning the different theoretical frameworks regarding the basis of psychiatric neuropathology and specifically their applicability to the field of neuroprotection. The different classification possibilities of neuroprotective candidates are also discussed. Finally, we will propose using a separate term in an attempt to differentiate psychiatric neuroprotection from other forms of neuroprotection - psychoprotection.